AIMS In the EMPA-REG OUTCOME® trial, the sodium-glucose cotransporter 2 inhibitor empagliflozin when given in addition to standard care improved cardiovascular (CV) and renal outcomes, and reduced mortality. Trial participants were on a variety of glucose-lowering therapies at baseline, some of which could potentially affect CV risk. This analysis investigated whether the use of background diabetes therapy affected the risk of CV death, hospitalizations for heart failure, and progression of chronic kidney disease, among patients treated with empagliflozin. MATERIALS AND METHODS Patients meeting inclusion and exclusion criteria were randomized to placebo, empagliflozin 10 mg or empagliflozin 25 mg; glucose-lowering therapy was to remain unchanged for 12 weeks and then adjusted to achieve glycaemic control according to local guidelines. Differences in risk of cardio-renal outcomes between empagliflozin and placebo by baseline use of metformin, sulphonylurea (SU) and insulin were assessed using a Cox proportional hazards model. RESULTS Of 7020 eligible patients, 74% were receiving metformin, 43% SU and 48% insulin at baseline (each alone or in combination); the most common regimens were metformin plus SU (20%) and metformin plus insulin (20%). Empagliflozin reduced the risk of CV death irrespective of the use of: metformin [with: hazard ratio (HR) 0.71 (95% confidence interval, CI, 0.54-0.94); without: 0.46 (0.32-0.68); Pinteraction = 0.07]; SU [with: HR 0.64 (0.44-0.92); without: 0.61 (0.46-0.81); Pinteraction = 0.85]; or insulin [with: HR 0.63 (0.46-0.85); without: 0.61 (0.44-0.85); Pinteraction = 0.92]. Reductions in three-point major adverse CV events, hospitalizations for heart failure, and all-cause mortality were consistent across subgroups of baseline therapies. Empagliflozin reduced the risks of incident or worsening nephropathy versus placebo irrespective of the use of SU or insulin at baseline (Pinteraction > 0.05), but there was a greater reduction in this risk for patients not using metformin [HR 0.47 (95% CI 0.37-0.59)] versus those using metformin [HR 0.68 (95% CI 0.58-0.79)] at baseline (Pinteraction = 0.01). CONCLUSIONS The addition of empagliflozin to antihyperglycaemic regimens of patients with type 2 diabetes and CV disease consistently reduced their risks of adverse CV outcomes and mortality irrespective of baseline use of metformin, SU or insulin. For chronic kidney disease progression, there may be a larger benefit from empagliflozin in those patients who are not using metformin.

中文翻译：

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基线降糖治疗会影响依格列净的心血管和肾脏益处吗？

目的在EMPA-REGOUTCOME®试验中，除标准护理外，给予钠-葡萄糖共转运蛋白2抑制剂依帕格列净可改善心血管（CV）和肾脏结局，并降低死亡率。试验参与者在基线时接受了多种降糖治疗，其中一些可能会影响心血管风险。这项分析调查了使用依帕列净治疗的患者中使用背景糖尿病治疗是否会影响心血管死亡风险，心力衰竭住院和慢性肾脏疾病的进展。材料和方法将符合入组和排除标准的患者随机分为安慰剂，依帕列净10 mg或依帕列净25 mg。降糖疗法应保持12周不变，然后根据当地指南进行调整以实现血糖控制。使用Cox比例风险模型评估了基线使用二甲双胍，磺脲类药物（SU）和胰岛素时，依格列净与安慰剂之间的心脏肾结局风险差异。结果在7020名合格患者中，有74％在基线时（单独或联合使用）接受二甲双胍，43％SU和48％胰岛素治疗。最常见的方案是二甲双胍加SU（20％）和二甲双胍加胰岛素（20％）。依帕格列净降低了CV死亡的风险，无论是否使用：二甲双胍[[具有：危险比（HR）0.71（95％置信区间，CI，0.54-0.94）；没有：0.46（0.32-0.68）; 互动= 0.07]；SU [with：HR 0.64（0.44-0.92）; 没有：0.61（0.46-0.81）; 互动= 0.85]；或胰岛素[HR：0.63（0.46-0.85）；不包含：0.61（0.44-0.85）；互动= 0.92]。减少三点主要不良CV事件，心力衰竭的住院治疗和全因死亡率在基线治疗的亚组之间是一致的。与基线时使用SU或胰岛素相比，Empagliflozin与安慰剂相比，降低了发生或恶化肾病的风险（交互作用> 0.05），但对于未使用二甲双胍的患者，这种风险的降低更大[HR 0.47（95％CI 0.37- 0.59）]与基线时使用二甲双胍[HR 0.68（95％CI 0.58-0.79）]的情况（互动= 0.01）。结论在2型糖尿病和CV疾病患者的抗高血糖治疗方案中加入依帕格列净后，无论使用二甲双胍，SU或胰岛素的基线剂量如何，均可持续降低其不良CV结果和死亡率的风险。对于慢性肾脏疾病的进展，